TETRAHEDRON LETTERS Tetrahedron Letters 40 (1999) 1669- 1672 Pergamon Synthesis of ~.Alkoxy ~-AminoAcid Esters Said Boukhris, Abdelaziz Souizi * Laboratoirede Synth~se Organique et d'Agrochimie, l~parternent de Chimie. Facult6 des Sciences. Universit6 Ibn Tofail.B.P 133-K6nitra (Maroc) Received 23 October 1998; accepted 2 January 1999 Abstract : [3-Alkoxy ~x-aminoacid esters and N-hydroxya-aminoesters are obtained by the reduction of easilyaccessible~-oximino esters. © 1999Published by EIsevierScienceLtd. All rights reserved. o~-Aminoacids play an important role in different areas, 1 e.g. as enzyme inhibitors, antibacterial agents, neuroactive compounds, pharmaceutical starting materials, herbicides and fungicides. However, 13- hydroxylated o~-aminoacids are biological compounds of major importance. They are components of various peptides possessing a wide range of biological activities such as antibiotic and immunosuppressive properties. In addition, two l~-hydroxylated c~-aminoacids are present in vancomycine which is a widely used antibiotic in the treatment of methicillin-resistant Staphylococcus aureus. 2-3 These or-amino [~-hydroxy acids have been described by Evans4 and Rao 5 et al.. A variety of approaches have been developped for their synthesis : several methods based on nucleophilic opening of epoxides, 6 on electrophilic amination 7 or asymmetric hydrogenation of N-protected m-amino [3-keto esters. 8 However, the synthesis of 13-alkoxy ~-aminoacid esters has not been well investigated to date. In this paper, we will describe the synthesis of such compounds starting from the t~-oximino esters 1. cc-Oximino acids are particularly useful precursors of m-amino acids. Reduction under a variety of conditions can produce either the corresponding N-hydroxy ~-aminoacids derivatives or the parent o~-amino acid itself. 9-10 We report that 13-alkoxy~-aminoacid esters can be prepared directly by reduction of easily accessible [3-alkoxy o~-oxirnino esters 11 with a buffered combination of titanium (III) chloride and sodium borohydride. Indeed, combination of titanium (HI) chloride and sodium borohydride in aqueous solution has been shown to be effective for the reduction of a sugar-derived oxime to the corresponding amino sugar.12 This prompts us to report on our reductions of c~-oximino esters la-i to 13-alkoxy~-aminoacid esters 2a-i. o"c °" O2 R1 TiCL3/NaBH 4 L-Tartaric acid X,,~ NHR 3 ~ C O 2 R1 H OR" or Py-BH3 Scheme 1 0040-4039/99/$ - see front matter © 1999 Published by Elsevier Science Ltd. All rights reserved. PII: S0040-4039(99)00061 - 1